Studies in patients with idiopathic inflammatory bowel disease (IBD) have implicated the immune system as important in the pathogenesis of these disorders. However, the origin of the autoimmune phenomona described in IBD and their importance in actually causing disease have been difficult to study in patients. The specific aim of this research is to test the hypothesis that an immune response to a gut organ-specific antigen (RGCG, RCG) can be etiologic for gastrointestinal inflammatory lesions seen in experimentally immunized animals; to identify the precise immunopathological mechanism(s) and underlying immuno-regulatory abnormalities responsible for such lesions in susceptible strains; and to study, in vitro, the mode of induction (a la Orgad and Cohen, 1971) of these responses by identifying, in serum, factors which inhibit immune recognition of gut organ-specific antigens. Methods to be employed will include: adoptive transfer of cells or serum from RCGC- (CG-) immune rats--to rigorously prove immunological causation of disease; functional/surgical lymphoid ablation experiments (adult thymectomy and aging, B-lymphocyte suppression with -specific sera)--to determine the precise immunological mechanism responsible for enteritis/colitis in immune rats; lymphocyte mixing experiments for detection of antigen-specific suppressor T lymphocytes as well as radioimmunoassay for circulating organ-specific antigen--to elucidate underlying immunoregulatory factors responsible for susceptibility to disease induction; assays of humoral immunity (passive hemagglutination and radioimmunoassay) as well as cell-mediated immunity (51Cr cellular cytotoxicity)--to determine whether autoimmune responses correlate with the onset, duration, and severity of gut cell damage in immunized as well as in parasite-infected rats; and the in vitro methods of Orgad and Cohen to determine the mechanism(s) responsible for maintaining natural tolerance to gut self antigen.